Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in rectal cancer treated with neoadjuvant concurrent chemoradiation: a meta-analysis and pooled-analysis of acute toxicity.

BACKGROUND: To compare the acute gastrointestinal (GI) and genitourinary (GU) toxicity profiles between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) using meta-analysis and pooled-analysis from published articles. METHODS: Literature search was performed in PubMed and EMBASE from inception to March 2017. The odd ratios (ORs) were calculated and random effects model was used for meta-analysis. Chi-square or Fisher's exact test was performed for the pooled-analysis. RESULTS: Six studies including a total of 859 patients met the inclusion criteria. Most patients (98.7%) received NCRT. In the meta-analysis, IMRT reduced grade ≥ 2 acute overall GI toxicity, diarrhea and proctitis with ORs of 0.38, 0.32 and 0.60, respectively (all P < 0.05), compared to 3DCRT. IMRT also reduced acute grade ≥ 3 proctitis compared to 3D-CRT (OR, 0.24; P = 0.03). No significant heterogeneity or publication bias was detected. In the pooled-analysis, IMRT reduced the incidence of grade ≥ 2 acute overall GI toxicity, diarrhea, proctitis and GU toxicity (all P < 0.05). Moreover, lower incidence of grade ≥ 3 acute overall GI toxicity, diarrhea and proctitis were observed in the patients treated with IMRT (all P < 0.05). CONCLUSIONS: IMRT significantly reduced acute toxicity in locally advanced rectal cancer patients treated with NCRT compared to 3DCRT.

Induction Chemotherapy Reduces Patient-reported Toxicities During Neoadjuvant Chemoradiation with Intensity Modulated Radiotherapy for Rectal Cancer.

BACKGROUND: Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had received induction chemotherapy versus those who did not. PATIENTS AND METHODS: We reviewed records of patients with locally advanced rectal cancer who were treated with CRT between September 2009 and October 2014, and who had completed ≥ 4 PRO assessments during treatment. Clinician- and patient-reported toxicities were collected each week during treatment. We fit binomial generalized linear models to maximum toxicity scores across all patients' visits. RESULTS: Of 123 patients with ≥ 4 PRO assessments, 87 (71%) patients reported a clinically meaningful PRO score of 3 or higher for diarrhea, and 91 (74%) patients reported a PRO score of ≥ 3 for urgency, during 1 or more weeks of treatment, corresponding to 'very frequent' or worse. Of 116 patients who had also completed ≥ 4 clinician-reported assessments for descriptive analysis, clinically significant diarrhea (Common Terminology Criteria for Adverse Events grade ≥ 2) was reported in 9% of patients, and grade 2 proctitis and cystitis were reported in 20% and 4%, respectively. Eighty-four (68%) patients had undergone induction chemotherapy prior to CRT. Patients who received induction chemotherapy had 68% lower odds of experiencing significant urgency (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.95; P = .04), 76% lower odds of bleeding (OR, 0.24; 95% CI, 0.1-0.62; P < .01), and 75% lower odds of tenesmus (OR, 0.25; 95% CI, 0.11-0.6; P < .01) versus those treated with upfront CRT. CONCLUSION: Based on PROs, a high proportion of patients experienced clinically significant symptoms during pelvic CRT, with diarrhea and urgency being most commonly reported. This appears to be under-reported on clinician-reported assessments. Delivery of induction chemotherapy was associated with lower odds of experiencing urgency, bleeding, and tenesmus on PROs during subsequent CRT, with no significant impact on diarrhea and rectal pain.

Acute toxicity with intensity modulated radiotherapy versus 3-dimensional conformal radiotherapy during preoperative chemoradiation for locally advanced rectal cancer.

BACKGROUND AND PURPOSE: We examined acute toxicity profiles and outcomes among rectal cancer patients treated with pre-operative chemoradiation using intensity modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3DCRT) to identify predictive clinical factors associated with increased acute toxicity. MATERIAL AND METHODS: We retrospectively reviewed records of 301 consecutive rectal cancer patients treated with pre-operative chemotherapy and radiotherapy (median dose 5000cGy) at our institution between 2007 and 2014. RESULTS: Of the 301 patients, 203 (67.4%) were treated with IMRT and 98 (32.6%) with 3DCRT. Significantly more patients experienced ⩾grade 2 diarrhea in the 3DCRT group compared to the IMRT group (22% vs 10%, p=0.004), and those who received 3DCRT had 2.7 times greater odds of a higher diarrhea score than those on IMRT, even after adjusting for patient characteristics and chemotherapy (OR 2.71, p=0.01) Fewer patients experienced grade 2 genitourinary toxicity in the IMRT group (6% vs 13% 3DCRT, p=0.04) and there was a trend toward decreased grade 2 proctitis in the IMRT group (22% vs 32% 3DCRT, p=0.07). Patients over the age of 55 had 45% lower odds of proctitis than patients younger than 55. CONCLUSION: The use of IMRT significantly reduced grade ⩾2 diarrhea and GU toxicity during chemoradiation. Younger patients were more likely to report grade 2 or higher proctitis.